- ASCENT, an international phase 3 open-label trial, involved 529 patients with relapsed/refractory metastatic triple-negative breast cancer in which sacituzumab govitecan was compared with physician-choice standard chemotherapy
- In both the subgroup of patients without brain metastases (n=468) and the full population, sacituzumab govitecan was superior to chemotherapy with respect to progression-free survival (HR, 0.41) and overall survival (HR, 0.48; P<0.001 for both)
- Survival benefits with sacituzumab govitecan was seen in all prespecified subgroups, including patients ages 65 and older, those with more than three previous therapies, and those previously treated with a PD-1 or PD-L1 inhibitor
- The most clinically relevant grade 3 or 4 adverse events with sacituzumab govitecan were neutropenia and diarrhea, which were managed with established supportive care measures
- Sacituzumab govitecan is now fully approved for adults with unresectable locally advanced or metastatic triple-negative breast cancer who have received two or more prior systemic therapies, at least one of them for metastatic disease
Sacituzumab govitecan (SG), a Trop-2–directed antibody–drug conjugate, received accelerated approval from the FDA in April 2020 for treatment of metastatic triple-negative breast cancer. The approval was based on a phase 1/2 trial published in Annals of Oncology. Full approval was conditional on the results of a phase 3 trial.
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That trial has now been completed and confirmed the significant survival benefit of SG over physician-choice chemotherapy. Aditya Bardia, MD, MPH, director of Precision Medicine in the Center for Breast Cancer at the Massachusetts General Hospital Cancer Center, and colleagues report the phase 3 data in The New England Journal of Medicine.
The open-label ASCENT trial enrolled 529 patients with relapsed/refractory triple-negative breast cancer between November 2017 and September 2019 at 88 sites in seven countries.
Patients were randomly assigned 1:1 to receive SG (10 mg/kg on days 1 and 8 of each 21-day cycle) or single-agent chemotherapy selected by their physician before randomization: eribulin, vinorelbine, capecitabine or gemcitabine.
At the data cutoff on March 11, 2020, the median follow-up was 17.7 months. The primary endpoint, progression-free survival (PFS) in patients without brain metastases (n=468), was 5.6 months with SG and 1.7 months with chemotherapy (HR, 0.41; P<0.001).
- Median overall survival (OS)—12.1 vs. 6.7 months (HR, 0.48; P<0.001)
- Median PFS in the full population—4.8 vs. 1.7 months (HR, 0.43; 95% CI, 0.35–0.54)
- Median OS in the full population—11.8 vs. 6.9 months (HR, 0.51; 95% CI, 0.41–0.62)
The most clinically relevant grade 3/4 adverse events with SG were neutropenia (7%) and diarrhea (10%, all grade 3). 49% of patients treated with SG versus 23% of those on chemotherapy received growth-factor support.
Serious treatment-related adverse events (AEs) were reported for 15% of SG-treated patients and 8% in the chemotherapy group. AEs leading to treatment discontinuation occurred in 5% of each group. No treatment-related death was reported in the SG group; one chemotherapy recipient died of neutropenic sepsis.
The FDA has fully approved SG for adults with unresectable locally advanced or metastatic triple-negative breast cancer who have received two or more prior systemic therapies, at least one of them for metastatic disease.
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